Striking changes in the time course of myocardial contraction have been documented during and following brief periods of ischemia or hypoxia. These studies have been conducted in whole tissue preparations and have allowed only partial delineation of the mechanisms underlying these changes in mechanics. Recent technical advances have allowed the more detailed study of these vents at the single cell level. A special chamber, developed in our laboratory, was employed to study contraction in single cells during and after brief periods of profound hypoxia (pO2<.02 torr). Rat ventriculocytes, loaded with the calcium-sensitive fluorescent probe indo-1, showed no early failure of contraction upon exposure to hypoxia, however marked changes in the timing of cell contraction and relaxation occurred early during hypoxia and at reoxygenation following brief hypoxia (10 minutes at 23degrees C). During hypoxia time to peak contraction (TPK) and time 50% relaxation (RT50) were abbreviated without a significant change in the time to 90% relaxation (RT90). The timing of the calcium transient was unaffected. At reoxygenation TPK, RT50 and RT90 were markedly prolonged again without any change in the timing of the calcium transient. Simultaneous measurement of the action potential and contraction in current-clamped cells showed similar mechanical changes without a change in the AP. We have recently documented a transient rebound intracellular alkalosis (using the pH sensitive fluorescent probe "SNARF-1) which occurs at reoxygenation and may contribute to the slowing of relaxation seen it reoxygenation by slowing myofilament relaxation kinetics.